Project Summary: The neural circuitry that encodes and mediates the establishment of cue-reward associations, an adaptive process that is essential for survival, likely becomes dysfunctional in neuropsychiatric illnesses such as drug addiction. While the full encoding of cue-reward associations require a distributed network of brain nuclei acting in concert to orchestrate behavioral output, neurons in ventral tegmental area and upstream circuits in cortex and hypothalamus are thought to play an important role in reward prediction and assigning incentive salience to environmental cues such as those that become associated with repeated drug use. In this application, we propose to state of the art deep brain two-photon imaging in awake and behaving mice to study how the encoding properties within these circuits emerge and are altered during primary reward exposure as well in associative learning. These experiments will provide important mechanistic information to explain how reward circuits encode and control the development and expression of cue-reward associations relevant to addiction.